Piperidine analogues of D-galactose as potent inhibitors of a-galactosidase: Synthesis by stannane-mediated hydroxymethylation of 5-azido-l,4-lactones. Structural relationships between D-galactosidase and L-rhamnosidase inhibitors

The syntheses of the polyhydroxylated piperidines deoxygalactonojirimycin 2, homogalactonojirimycins 7 and 9, and other 2,6-iminoheptitol derivatives, including an analogue of L-altropyranose, are reported. 5-Azidoaldono1,4-lactones undergo chain extension to afford azido lactols by the addition of a hydroxymethyllithium species 18, generated by transmetallation of a protected stannylmethanol derivative 17. Hydrogénation results in azide reduction with subsequent intramolecular reductive amination to give piperidine ring systems. The deprotected iminogalactopyranose analogues are potent and selective a-galactosidase inhibitors. Observations on the structural features determining selectivity of inhibition of a-galactosidases over naringinase (L-rhamnosidase) are also reported. © The Royal Society of Chemistry 1999.